Micro-compartment plays a key role in cellular metabolic functions, which increases the overall activity and specificity of encapsulated enzyme pathways. Proteins that are spatially-confined on a membrane or within a vesicle experience a unique microenvironment that can alter water dynamics, local electrostatic interactions, variation in the solvent solubility and molecular crowding. The ability to mimic and exert control over spatial confinement could translate biochemical pathways into a variety of noncellular applications, ranging from diagnostics and drug delivery to the production of high-value chemicals and smart materials. Here, we described a simple and robust strategy for the DNA nanocage-templated encapsulation of metabolic enzymes with high assembly yield and controlled packaging stoichiometry. As shown in <b>Fig. 1a</b>, DNA nanocaged enzymes were observed with increased turnover numbers for catalyzing substrate conversion. The distal polyanionic surfaces of DNA nanocages were suggested to enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. Alternatively, we also developed a DNA-crowded enzyme complex by directly growing long double-stranded DNA “hair” on enzyme surface for boosting and stabilizing enzyme activity (<b>Fig. 1b</b>). In collaboration with drug delivery team, we tested the cellular delivery of DNA-crowded enzyme nanoparticles, which showed increased cellular uptake yield. DNA-crowded enzyme complexes show boosted substrate turnover numbers, and increased stabilities against various storage conditions. They could be potentially scaled up for applications in biomaterials and biotechnology.

DNA-crowded enzyme complexes with controlled spatial confinement and improved function

2019 Spring National Meeting

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